Live Donor Liver Transplantation: A Life Saving Option for End - - PDF document

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Live Donor Liver Transplantation: A Life Saving Option for End - - PDF document

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March 12, 2019 Live Donor Liver Transplantation: A Life Saving Option for End Stage Liver Disease Abhi Humar, MD Clinical Director, Thomas E. Starzl Transplantation Institute 1 PITTSBURGHTHE BIRTHPLACE OF LIVER TRANSPLANTATION

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March 12, 2019 1

Live‐Donor Liver Transplantation: A Life‐Saving Option for End‐Stage Liver Disease

Abhi Humar, MD Clinical Director, Thomas E. Starzl Transplantation Institute

1

  • Liver transplantation: one of the miracles of

modern medicine

  • Liver transplant is now established as the only

definitive treatment for end‐stage liver disease (ESLD)

  • Survival following liver transplant

 1 year survival: 87 – 93%  5 year survival: > 75%

PITTSBURGH—THE BIRTHPLACE OF LIVER TRANSPLANTATION

2

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March 12, 2019 2

LIVER TRANSPLANTATION AT UPMC: AN ESTABLISHED LEGACY

1981

  • Dr. Starzl performs Pittsburgh’s first liver transplant,

establishing the country’s first liver transplant program.

1985

Over 600 liver transplants performed in a single year.

1989

Tacrolimus introduced as the new immunosuppressant drug.

1999

UPMC performs its first adult living‐donor liver transplant.

2017

UPMC performs more living‐donor liver transplants than deceased donor liver transplants.

2018

UPMC and Pitt establish the Immune Transplant and Therapy Center, which will work to reduce immunosuppressants. 3

CURRENT STATUS OF LIVER TRANSPLANT IN THE U.S.

2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Series2 Series3 Series1

Waiting List Living Donor tx Deceased donor tx 4

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March 12, 2019 3

CONSEQUENCES OF A WAITING LIST AND LIMITED RESOURCE

What does this mean for the individual patient needing a liver transplant?

  • 1. About a 15‐25% chance of never making it to transplant
  • 2. Longer waiting times before receiving a transplant
  • A more debilitated state by the time a transplant is performed
  • A longer and more difficult recovery time post‐transplant
  • 3. Not all patients that could benefit are listed or offered

transplant

5

PROBLEM: NOT ENOUGH LIVERS FOR ALL THE PEOPLE WHO NEED THEM

5 10 15 20 25 30 2012 2013 2014 2015 2016 2017

Median Waiting Time

5 10 15 20 25 30 35 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

PAPT Mean MELD Deceased Donor

PAPT MEAN MELD ‐ DECEASED DONOR Linear (PAPT MEAN MELD ‐ DECEASED DONOR)

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Patients in our local area are waiting longer and are sicker by the time they receive a transplant. Waitlist mortality of 25%.

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March 12, 2019 4

LDLT—A POSSIBLE SOLUTION FOR THE WAITING LIST PROBLEM

Possible because of 2 unique properties of our liver:

  • Extra capacity built in
  • Ability to regenerate

7

ADVANTAGES AND DISADVANTAGES OF LDLTX

  • Decrease waitlist mortality
  • Decreased waiting time
  • Transplant prior to recipient

becoming critically ill

  • Elective, non‐emergent
  • Minimal cold ischemia
  • Immunologic advantage
  • Adds to cadaver pool
  • Financial benefit
  • Short‐term risks to donor
  • Long‐term risks to donor
  • Increased incidence of biliary and

vascular complications

  • Decreased hepatic reserve

Advantages Disadvantages

8

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March 12, 2019 5

RESULTS WITH LIVER TRANSPLANT AT UPMC: LIVING VS DECEASED DONOR

9

P=0.03 Living Donor N=222 Deceased donor N=625 P value Median LOS 11 days 14 days 0.03 No intraop transfusion 48% 22% 0.01 1 year survival 91% 86% 0.02

TECHICAL OUTCOMES WITH LIVER TRANSPLANT AT UPMC: 2009‐2018 LIVING VS DECEASED DONOR

10

Living Donor N=226 Deceased donor N=632 P value Hepatic artery thrombosis 3.4% Portal venous complication 1.3% 0.32% P=0.12 Biliary complication 14.3% 11.5% P=0.20 3 month reoperation 29% 29% P=0.81

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March 12, 2019 6

  • Cost of transplant (from 6 months pretransplant to 1 year

posttransplant) was 30.8% cheaper in LDLT group (p<0.01)

  • Waitlist patients had an average of 2.7admissions/year to

hospital with charges for each hospital stay averaging $70k.

UPMC Living Donor Utilization/Cost Comparison

11 12

UPMC Living Donor Utilization/Cost Comparison

Deceased‐Donor Liver Transplant Recipient N=52 Living‐Donor Liver Transplant Recipient N=60

*Based on UPMC Transplant cases in CY 17 Pre‐transplant: 3.4 average radiology scans Post‐transplant: 12.0 average radiology scans .7 average ED visits .7 average GI procedures and surgeries Pre‐transplant: 2.6 average radiology scans Post‐transplant: 8.6 average radiology scans .5 average ED visits .2 average GI procedures and surgeries 25 percent reduction in outpatient labs

UPMC data shows cost benefits for living donors related to pre‐transplant radiology and post‐transplant radiology, ED visits, GI procedures and surgeries, and labs.

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March 12, 2019 7

CURRENT STATE OF LDLT IN THE U.S.

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100 200 300 400 500 600 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

# LDLT

UNDERUTILIZED: ONLY 401 LDLT PERFORMED IN THE ENTIRE U.S. IN 2018 THIS ACCOUNTED FOR 4.8% OF THE TOTAL NUMBER OF TRANSPLANTS.

DRAMATIC DIFFERENCE WITH USE OF LDLT AROUND THE WORLD

2 4 6 8 10 12 14 16 18 20 Korea Taiwan Hong Kong Japan Belgium Germany U.S.A. Italy

Living Donor Liver Transplants per Million People

2006 2010 2016

14

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March 12, 2019 8

ONLY 15 US CENTERS HAVE DONE >100 ALDLT Total

15 Number

  • f LDLT

(2018) Number

  • f

Centers ≥10 12 5‐9 15 1‐4 20

100 200 300 400 500 600 564 380 296 361 215 373 182 173 308 245

Chart Title

WHY HAVE THE NUMBER OF LDLTS REMAINED SO LOW IN THE U.S.?

  • Complex procedures that require great degree of technical

expertise from an entire team

  • Numerous regulations with significant consequences for center:

– UNOS, CMS, state

  • Donor complications/deaths that have been highly publicized
  • Risk for careers of specific team members
  • People don’t know or are misinformed!

16

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March 12, 2019 9

Lack of Awareness

17

Patients Providers Payors

Pediatric LDLT

Adult LDLT

UPMC STRONGLY BELIEVES IN THE VALUE OF LDLT TO HELP PATIENTS

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March 12, 2019 10

  • UPMC is the only center performing LDLT

in western PA

  • More than 50% of our transplants in 2017

and 2018 were with a living donor (national average 4.5%)

512 157 38 14 12 10 36

Liver TX Referrals By State, 1/2013‐12/2014 PA WV OH MD NY VA Other

UPMC STRONGLY BELIEVES IN THE VALUE OF LDLT TO HELP PATIENTS

19

NUMBER OF LDLT AT UPMC BY YEAR

10 20 30 40 50 60 70 80 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

# Adult LDLT # Pediatric LDLT 20

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March 12, 2019 11

LDLT AT UPMC COMPARED TO THE REST OF THE U.S.

21

10 20 30 40 50 60 70 80 71 29 26 23 16 13 10 10 10 10

In 2017, 20% of all LDLTs performed in the US were at UPMC

2017 LDLT US volume by center Total 2017 volume: 367

100 200 300 400 500 600

# LDLT

HIGHLY PUBLICIZED DONOR DEATH AND THE IMPACT

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March 12, 2019 12

DONOR RISK

6826 LDLT (Jan 2019)

6 donor deaths (0.10%) 3 donors received a LTX

National Data UPMC Data

  • No donor deaths
  • No cases of liver failure
  • Overall complication rate 19.5%
  • Major complication rate of

8.8%

  • Mean length of stay‐ 5.8 days
  • Overall complication 30%
  • Major complication 10%
  • Reoperation rate of 6.2%

– Early (<3 months)- 2.7% (bowel perforation, bleeding, SBO, negative lap) – Late (>3 months)- 3.5% (hernias)

  • Biliary leak/biloma: 3 (1.3%)- all managed with

percutaneous drainage +/- ERCP

  • Medical complications: UTI, pneumonia, c diff,

DVT/PE, wound infection, fever nyd, abdominal pain nyd, nerve injury.

DONOR OUTCOMES

24

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March 12, 2019 13

  • Recovery:

5‐7 days in hospital 4‐6 weeks desk job 10‐12 weeks physical job 80‐90% by 3 months post donation

DONOR SAFETY AND RECOVERY IS KEY

25

Live donor kidney transplant is the gold standard treatment for ESRD

  • Between 1999 and 2011 there were

25 kidney donor deaths within 3 months of donation.

  • There is a very slight increase in risk

for developing ESRD over time in kidney donors

  • No cases of late liver failure

reported after liver donation

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March 12, 2019 14

RESULTS WITH LIVER TRANSPLANT AT UPMC: LIVING VS DECEASED DONOR

27

P=0.03 Living Donor N=222 Deceased donor N=625 P value Median LOS 11 days 14 days 0.03 No intraop transfusion 48% 22% 0.01 1 year survival 91% 86% 0.02

SRTR PAPT LDLT GRAFT SURVIVAL RATE

28

Graft Survival‐ 1 year

www.optn.org

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March 12, 2019 15

OVERALL TRANSPLANT RATE AT UPMC HAS INCREASED AS A RESULT OF USE OF LDLT

29 www.optn.org

Waitlist Mortality is Starting to Decrease

30 www.optn.org

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March 12, 2019 16

Evolution of how we think about LDLT at our center

Initial recipient selection criteria:

  • Patients low on waiting list but with bad prognostic signs
  • Patients with liver tumors in and out of criteria
  • International patients

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RESULTS WITH LDLT FOR HIGH‐MELD PATIENTS

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Strategies to transplant high‐MELD patients:

  • Right lobe grafts
  • Young donors
  • Include MHV in the graft
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March 12, 2019 17

UNIVERSITY OF PITTSBURGH MEDICAL CENTER STARZL TRANSPLANTATION INSTITUTE LIVER TRANSPLANT POLICIES AND PROCEDURES POLICY LT‐CCA‐0415 LIVER TRANSPLANTATION IN PATIENTS WITH HILAR CHOLANGIOCARCINOMA UNIVERSITY OF PITTSBURGH MEDICAL CENTER STARZL TRANSPLANTATION INSTITUTE LIVER TRANSPLANT POLICIES AND PROCEDURES POLICY LT‐CCA‐0415 LIVER TRANSPLANTATION IN PATIENTS WITH METASTATIC COLORECTAL METASTASIS UNIVERSITY OF PITTSBURGH MEDICAL CENTER STARZL TRANSPLANTATION INSTITUTE LIVER TRANSPLANT POLICIES AND PROCEDURES POLICY LT‐CCA‐0415 LIVER TRANSPLANTATION IN PATIENTS WITH HCC BEYOND MILAN UNIVERSITY OF PITTSBURGH MEDICAL CENTER STARZL TRANSPLANTATION INSTITUTE LIVER TRANSPLANT POLICIES AND PROCEDURES POLICY LT‐CCA‐0415 LIVER TRANSPLANTATION IN PATIENTS WITH METASTATIC NEUROENDOCRINE AND OTHER RARE TUMORS 34

UPMC ABO‐I LIVE DONOR LIVER TX PROTOCOL

‐7 to ‐1 ‐21~‐14 LDLTx if anti‐ABO titer ≤ 1:8 +7 +21 Tacrolimus (8~12  10~15 ng/dl) 2~3 months MMF 1gm PO BID PLEX Rituximab (300 mg/m2) ‐9 PLEX Steroid taper ( 3‐month minimum)

Anti‐ABO Ab titers Initial evaluation Following each PLEX Anti‐ABO Ab titers Week 1: daily Weeks 2‐4: twice weekly Liver biopsy Post LDLTx months 1/3/12 Suspected AMR

PLEX for 1) anti‐ABO titer ≥ 64 2) suspicion of AMR. ‐3 IVIG for biopsy proven AMR

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March 12, 2019 18

Extended use of LDLT at the STI

  • Acute Alcoholic Hepatitis
  • HCC: Extended criteria
  • Cholangiocarcinoma
  • Jehovah's Witness: Bloodless surgery
  • ABO Incompatible LDLT
  • Unresectable colorectal metastases
  • International patients

35

  • Low/High‐MELD patients
  • Older recipients
  • Simultaneous liver‐kidney
  • Re‐do liver transplants
  • NET and other rare tumors
  • HIV recipients
  • Acute liver failure

A suitable LDLT is the first option for all of our patients

  • Current rules of allocation and MELD are appropriate for

utilization of a limited resource.

  • With a LDLT and 1 donor /1 recipient situation‐ These rules

don’t apply.

  • Criteria for LDLT should be based on ability to provide a survival

advantage.

  • LDLT is not the last resort but rather the first and best resort.

TIME TO CHANGE THE PARADIGM OF HOW WE THINK ABOUT LIVER DISEASE IN THE SETTING OF LDLT PROGRAM:

36

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March 12, 2019 19

RECIPIENT SELECTION CRITERIA AT UPMC

  • 1. Significant survival benefit with liver transplant vs.

best other therapy

  • 2. Suitable, willing living donor

37

Use of donor derived dendritic cells to induce immune tolerance:

  • Funded through ITTC by UPMC
  • Goal of study to remove long‐term immunosuppression from transplant patients

LDLT ALLOWS FOR UNIQUE RESEARCH OPPORTUNITIES

38

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March 12, 2019 20

KEYS TO SUCCESS

Strong living donor team:

  • Donor Surgeon
  • Transplant Hepatologist
  • Living Donor Nurse Coordinator
  • Transplant Social Workers
  • Transplant Financial Counselor
  • Independent Living Donor Advocate

39

EDUCATION & AWARENESS CAMPAIGN

  • Education about LDLT

and risks and benefits

  • Education about how to

find living donor

40

Patients and caregivers Physicians and

  • ther healthcare

workers Payors

  • Education about LDLT

risks and benefits

  • Education about

Suitability and indications

  • Education about LDLT

risks and benefits

  • Education about

financial benefits

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March 12, 2019 21 Physician Resources ‐ Educational Brochures and Lectures

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Patient Resources ‐ Educational Brochure and Video Series

42

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March 12, 2019 22 Patient Resources – Champion Program

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UPMC Champion Program (On‐going)

  • Champion workshops
  • Community info sessions
  • Champion support group
  • Town hall event
  • Champion toolkit
  • Champion ambassador

Champion Support Group Champion toolkit

“Get out of line” Campaign

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:30 Out of Line

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March 12, 2019 23

Data from Google Analytics

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2000 4000 6000 8000 10000 12000 14000 16000 Pre‐campaign Post‐campaign Average monthly national searches for "LDLT"

THE FUTURE: WHAT’S NEXT FOR LIVER TRANSPLANT

  • Eliminate the wait list
  • Educate physicians, payors, patients and

families

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March 12, 2019 24

OUR PATIENTS WILL TAKE US THERE

Terra & Amy

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